Feasibility of interstitial Doppler optical coherence tomography for in vivo detection of microvascular changes during photodynamic therapy

Introduction: Doppler optical coherence tomography (DOCT) is an emerging imaging modality that provides subsurface microstructural and microvascular tissue images with near histological resolution and sub-mm/ second velocity sensitivity. A key drawback of OCT for some applications is its shallow (1-3 mm) penetration depth. This fundamentally limits DOCT imaging to transparent, near-surface, intravascular, or intracavitary anatomical sites. Consequently, interstitial Doppler OCT (IS-DOCT) was developed for minimally-invasive in vivo imaging of microvasculature and microstructure at greater depths, providing access to deep-seated solid organs. Using Dunning prostate cancer in a rat xenograft model, this study evaluated the feasibility of IS-DOCT monitoring of microvascular changes deep within a tumor caused by photodynamic therapy (PDT). Materials and Methods: The DOCT interstitial probe was constructed using a 22 G (diameter similar to 0.7 mm) needle, with an echogenic surface finish for enhanced ultrasound visualization. The lens of the probe consisted of a gradient-index fiber, fusion spliced to an angle-polished coreless tip to allow side-view scanning. The lens was then fusion spliced to a single-mode optical fiber that was attached to the linear scanner via catheters and driven along the longitudinal axis of the needle to produce a 2D subsurface DOCT image. The resultant IS-DOCT system was used to monitor microvascular changes deep within the tumor mass in response to PDT in the rat xenograft model of Dunning prostate cancer. Surface PDT was delivered at 635 nm with 40 mW of power, for a total light 2 dose of 76 J/cm(2), using 12.5 mg/kg of Photofrin as the photosensitizer dose. Results: IS-DOCT demonstrated its ability to detect microvasculature in vivo and record PDT-induced changes. A reduction of detected vascular cross sectional area during treatment and partial recovery post-treatment were observed. Conclusions: IS-DOCT is a potentially effective tool for real-time visualization and monitoring of the progress of PDT treatments. This capability may play an important role in elucidating the mechanisms of PDT in tumors, pre-treatment planning, feedback control for treatment optimization, determining treatment endpoints and posttreatment assessments.